Quercetin protects necrotic insult and promotes apoptosis by attenuating the expression of RAGE and its ligand HMGB1 in human breast adenocarcinoma cells.

The receptor for advanced glycation end-products (RAGE) is a multiligand member of the immunoglobulin superfamily, which plays an important role in maintaining cellular homeostasis. It is normally expressed on immune cells, including macrophages, monocytes, dendritic cells and T cells to maintain homeostasis, but highly upregulated at sites of vascular pathology. Accumulating evidence suggest that the elevated expression of RAGE and its ligand HMGB-1 was found in various types of cancer. The accumulation of RAGE and its ligand high-mobility group box proteins-1 (HMGB1) activates complex signaling network for cell survival and evades apoptosis. Therefore, targeting the RAGE-mediated signaling could be the promising strategies for the therapeutic potential of cancer. This study was aimed to examine the biological potential of quercetin on the regulation of RAGE- and HMGB1-mediated activation of NF-κB and induction of apoptotic cell death in MCF-7 cells. Our findings demonstrate that quercetin inhibits the expression of RAGE and HMGB1 in MCF-7 cells. In addition, quercetin protects necrotic insult and augments apoptosis in MCF-7 cells. Taken together, these results suggest that quercetin plays an important role in modulating RAGE and HMGB1 signaling and induces apoptotic cell death in MCF-7 cells.